27 43

Cited 1 times in

German Cockroach Extract Induces Matrix Metalloproteinase-1 Expression, Leading to Tight Junction Disruption in Human Airway Epithelial Cells

Authors
 Kyung Eun Lee  ;  Hye Mi Jee  ;  Jung Yeon Hong  ;  Mi Na Kim  ;  Mi Seon Oh  ;  Yun Seon Kim  ;  Kyung Won Kim  ;  Kyu Earn Kim  ;  Myung Hyun Sohn 
Citation
 Yonsei Medical Journal, Vol.59(10) : 1222-1231, 2018 
Journal Title
 Yonsei Medical Journal 
ISSN
 0513-5796 
Issue Date
2018
Keywords
German cockroach ; airway epithelial cell ; asthma ; matrix metalloproteinase ; tight junction
Abstract
PURPOSE: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenance of the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellular matrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airway obstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) induces MMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). MATERIALS AND METHODS: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins were detected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance (TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while the levels of tight junction proteins and phosphorylation were determined using Western blotting. RESULTS: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interfering RNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfection with ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. An extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. CONCLUSION: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulated and influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeutic strategies for airway diseases.
Files in This Item:
T201804579.pdf.pdf Download
DOI
10.3349/ymj.2018.59.10.1222
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
김경원(Kim, Kyung Won) ORCID logo https://orcid.org/0000-0003-4529-6135
김규언(Kim, Kyu Earn)
김미나(Kim, Mina) ORCID logo https://orcid.org/0000-0002-1675-0688
손명현(Sohn, Myung Hyun) ORCID logo https://orcid.org/0000-0002-2478-487X
홍정연(Hong, Jung Yeon) ORCID logo https://orcid.org/0000-0003-0406-9956
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166738
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse